Novel synthetic analogs of sphingolipids
AssigneesHadasit Medical Research Services and Development Ltd., Yissum Research Development Company of the Hebrew University of Jerusalem
InventorsArie Dagan, Shimon Slavin, Shimon Gatt, Jeremy Zahavi
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Abstract
The present invention provides new ceramide analogs indicated as the compounds of formula (II). These novel analogs exhibit a significant anti cancerous effect and are therefore provided as a pharmaceutical composition for treating cell proliferative diseases, neurodegenerative disorders, metabolism-associated conditions, infectious diseases, and immune-related disorders. The invention further provides combined compositions and kits combining the novel ceramide analogs of formula (II) with an additional therapeutic agent.
Claims23
A compound of formula (II)
- wherein
- X represents a hydrogen atom or OH;
- Y represents
- wherein R6 represents a C2-20 linear or branched alkyl or alkenyl chain which may be optionally substituted with hydroxyl;
- and
- W represents a hydrogen atom or C1-20 linear or branched alkyl or alkenyl chain which may be optionally substituted with hydroxyl,
- or a pharmaceutically acceptable salt or isomer thereof.
A composition comprising a combination of at least one compound of formula (II) or a pharmaceutically acceptable salt or isomer thereof, and at least one additional therapeutic agent, optionally further comprising at least one pharmaceutically acceptable carrier, diluent, excipient and/or additive.
A kit for providing a therapeutic effect in a subject in need thereof comprising:
- a. at least one compound of formula (II) or a pharmaceutically acceptable salt or isomer or other derivative thereof, or any combination or mixture thereof, and a pharmaceutically acceptable carrier or diluent, optionally, in a first unit dosage form;
- b. at least one therapeutic agent selected from topoisomerase inhibitors, nucleic acids antimetabolites, and antimitotic agents and a pharmaceutically acceptable carrier or diluent, optionally, in a second unit dosage form;
- c. container means for containing said first and second dosage forms;
- and
- d. instructions for use.
A method for the treatment of a subject suffering from a pathological disorder comprising the step of administering to said subject a therapeutically effective amount of the compound of Formula II, or any composition, combined composition or kit thereof, said disorder being any one of a proliferative disorders, immune-related disorders, neurodegenerative disorders, infectious diseases and metabolism-associated conditions.
A method for the treatment of a pathologic disorder selected from the group consisting of proliferative disorders, immune-related disorders, neurodegenerative disorders, infectious diseases and metabolism-associated conditions and combinations thereof, comprising administering to a subject a therapeutically effective amount of compound of formula (I):
- wherein
- R represents a hydrogen atom, or phenyl optionally substituted by nitro, amino, alkylamino, acylamino, —NHC(S)NH-alkyl, sulfonylamido-alkyl,
- adamantane wherein n is an integer of from 1 to 20, —NH-adamantane;
- X represents a hydrogen atom or OH;
- Y represents
- wherein n is an integer of from 0 to 6, and wherein R6 represents a C2-20 linear or branched alkyl or alkenyl chain which may be optionally substituted with hydroxyl,
- wherein R1, R2 and R3, independently represent C1-C6 alkyl or C1-C6 alkenyl;
- Z represents a hydrogen atom, —OH, a mono- or disaccharide, a monosaccharide sulfate, or choline phosphate;
- and
- W represents a hydrogen atom, or C1-20 linear or branched alkyl or alkenyl chain which may be optionally substituted with hydroxyl,
- with the proviso that if R is hydrogen, Y is not
Dependencies are inferred from the claim text.